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Neuroprotection and funcional recuparation after radicular repair and thymosin beta 4 treatment

Grant number: 24/16278-2
Support Opportunities:Scholarships in Brazil - Master
Start date: August 01, 2025
End date: May 31, 2027
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Caio Gonçalves do Amaral
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Damage to the spinal cord can be caused by a variety of factors, from automobile and domestic accidents to issues related to violence involving firearms and bladed weapons, generally resulting in irreversible sequelae. The loss of communication or activity of motor and sensory neurons, which can be partial or total, culminates in the reduction or loss of mobility and sensitivity of the patient, and can also lead to the development of neuropathic pain, which has a negative impact on their quality of life. Another result of nerve tissue damage is the expansion of the damage due to the local inflammatory reaction, which causes considerable toxicity to the neurons, culminating in an increase in the radius of the lesion. In addition to the damage itself, the tissue healing process can end in fibrosis, which hinders local blood circulation and creates physical obstructions, with the presence of molecules that inhibit axonal growth, leading to a worse clinical outcome. With the aim of developing a therapy to help in these cases, Thymosin ¿4 (T¿4), an endogenous peptide with antifibrotic, immunomodulatory, angiogenic and cytoprotective activity, is a promising candidate. Other research has shown it to be effective in treating fibrotic processes in different organs such as the kidneys and liver, as well as helping to regenerate tissue damage. Based on its previously documented effects, the aim of this study is to observe its neuroprotective potential in spinal cord injuries. Using C57BL/6jUnib mice as a model, spinal motor roots (L4-L6) will be avulsed, followed by reimplantation using fibrin biopolymer, previously studied in our laboratory. T¿4 will be administered intraperitoneally after the surgeries, at 30', 24h and 48h. Nerve samples will be collected at 1 and 8 weeks after the procedure for analysis by Nissl staining and immunohistochemistry, obtaining data related to neuronal survival and gliosis. During this period, behavioral gait information will also be collected using the CatWalk system (walking track test), providing a broad view of its possible application in subsequent clinical trials.

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